RESUMO
INTRODUCTION: Fetal sex affects fetal and maternal health outcomes in pregnancy, but this connection remains poorly understood. As the placenta is the route of fetomaternal communication and derives from the fetal genome, placental gene expression sex differences may explain these outcomes. OBJECTIVES: We utilized next generation sequencing to study the normal human placenta in both sexes in first and third trimester to generate a normative transcriptome based on sex and gestation. STUDY DESIGN: We analyzed 124 first trimester (T1, 59 female and 65 male) and 43 third trimester (T3, 18 female and 25 male) samples for sex differences within each trimester and sex-specific gestational differences. RESULTS: Placenta shows more significant sexual dimorphism in T1, with 94 T1 and 26 T3 differentially expressed genes (DEGs). The sex chromosomes contributed 60.6% of DEGs in T1 and 80.8% of DEGs in T3, excluding X/Y pseudoautosomal regions. There were 6 DEGs from the pseudoautosomal regions, only significant in T1 and all upregulated in males. The distribution of DEGs on the X chromosome suggests genes on Xp (the short arm) may be particularly important in placental sex differences. Dosage compensation analysis of X/Y homolog genes shows expression is primarily contributed by the X chromosome. In sex-specific analyses of first versus third trimester, there were 2815 DEGs common to both sexes upregulated in T1, and 3263 common DEGs upregulated in T3. There were 7 female-exclusive DEGs upregulated in T1, 15 female-exclusive DEGs upregulated in T3, 10 male-exclusive DEGs upregulated in T1, and 20 male-exclusive DEGs upregulated in T3. DISCUSSION: This is the largest cohort of placentas across gestation from healthy pregnancies defining the normative sex dimorphic gene expression and sex common, sex specific and sex exclusive gene expression across gestation. The first trimester has the most sexually dimorphic transcripts, and the majority were upregulated in females compared to males in both trimesters. The short arm of the X chromosome and the pseudoautosomal region is particularly critical in defining sex differences in the first trimester placenta. As pregnancy is a dynamic state, sex specific DEGs across gestation may contribute to sex dimorphic changes in overall outcomes.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Placenta , Caracteres Sexuais , Humanos , Feminino , Gravidez , Masculino , Placenta/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Adulto , Transcriptoma , Terceiro Trimestre da Gravidez/genética , Análise de Sequência de RNA , Primeiro Trimestre da Gravidez/genética , Primeiro Trimestre da Gravidez/metabolismoRESUMO
The placenta, composed of chorionic villi, changes dramatically across gestation. Understanding differences in ongoing pregnancies are essential to identify the role of chorionic villi at specific times in gestation and develop biomarkers and prognostic indicators of maternal-fetal health. The normative mRNA profile is established using next-generation sequencing of 124 first trimester and 43 third trimester human placentas from ongoing healthy pregnancies. Stably expressed genes (SEGs) not different between trimesters and with low variability are identified. Differential expression analysis of first versus third trimester adjusted for fetal sex is performed, followed by a subanalysis with 23 matched pregnancies to control for subject variability using the same genetic and environmental background. Placenta expresses 14,979 polyadenylated genes above sequencing noise (transcripts per million > 0.66), with 10.7% SEGs across gestation. Differentially expressed genes (DEGs) account for 86.7% of genes in the full cohort [false discovery rate (FDR) < 0.05]. Fold changes highly correlate between the full cohort and subanalysis (Pearson = 0.98). At stricter thresholds (FDR < 0.001, fold change > 1.5), there remains 50.1% DEGs (3353 upregulated in first and 4155 upregulated in third trimester). This is the largest mRNA atlas of healthy human placenta across gestation, controlling for genetic and environmental factors, demonstrating substantial changes from first to third trimester in chorionic villi. Specific differences and SEGs may be used to understand the specific role of the chorionic villi throughout gestation and develop first trimester biomarkers of placental health that transpire across gestation, which can be used for future development of biomarkers for maternal-fetal health.
Assuntos
Placenta , Primeiro Trimestre da Gravidez , Terceiro Trimestre da Gravidez , RNA Mensageiro , Transcriptoma , Humanos , Feminino , Gravidez , Terceiro Trimestre da Gravidez/genética , Placenta/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Primeiro Trimestre da Gravidez/genética , Adulto , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
Este manual está dirigido a la partera tradicional para ayudarle a que haga su trabajo como toda una profesional y así forme parte del gran ejército de cuidado y promoción a la salud. Las parteras tradicionales deben ver a las embarazadas regularmente toda la gestación y también deben capacitarse para atender el parto en condiciones de gran limpieza y aplicar varias medidas que son importantes para la madre y el recién nacido. La tarea no termina allí, ya que las parteras deben hacer la revisión de la madre en el puerperio, fomentar la alimentación al pecho, ver que el niño vaya creciendo normalmente y que reciba sus vacunas. Asimismo, la partera debe aconsejar a la pareja del beneficio que tiene la planificación familiar tanto para la salud de la madre como el bienestar del niño. Por ello el trabajo que realizan las parteras tradicionales es de gran importancia para contribuir a asegurar la salud de la población que vive en el campo y que necesita mucho de sus cuidados